Department of Biomedical Sciences, Section of Cytomorphology, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato, Italy.
Department of Life and Environmental Sciences, Section of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato, Italy.
Int J Mol Sci. 2022 Nov 30;23(23):14995. doi: 10.3390/ijms232314995.
The present work was undertaken to investigate the effects of acute forced swimming (FS) on the levels of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (trkB) proteins in: the ventral tegmental area (VTA); the nucleus accumbens (Acb) shell and core compartments; and the anterior cingulate (ACg), prelimbic (PL) and infralimbic (IL) territories of the prefrontal cortex of genetic models of vulnerability (RLA, Roman low-avoidance rats) and resistance (RHA, Roman high-avoidance rats) to stress-induced depression. We report for the first time that FS induced very rapid and distinct changes in the levels of BDNF and trkB proteins in different areas of the mesocorticolimbic system of RHA and RLA rats. Thus, (1) in the VTA and Acb core, FS elicited a significant increase of both BDNF- and trkB-LI in RHA but not RLA rats, whereas in the Acb shell no significant changes in BDNF- and trkB-LI across the line and treatment were observed; (2) in RLA rats, the basal levels of BDNF-LI in the IL/PL cortex and of trkB-LI in the ACg cortex were markedly lower than those of RHA rats; moreover, BDNF- and trkB-LI in the IL/PL and ACg cortex were increased by FS in RLA rats but decreased in their RHA counterparts. These results provide compelling evidence that the genetic background influences the effects of stress on BDNF/trkB signaling and support the view that the same stressor may impact differently on the expression of BDNF in discrete brain areas.
本研究旨在探讨急性强迫游泳(FS)对易感性(RLA,罗曼低回避大鼠)和抵抗性(RHA,罗曼高回避大鼠)遗传模型的腹侧被盖区(VTA)、伏隔核(Acb)壳和核区以及前额叶皮质的前扣带(ACg)、额前皮质的外侧(PL)和内侧(IL)区域中脑源性神经营养因子(BDNF)和酪氨酸激酶受体 B(trkB)蛋白水平的影响。我们首次报道,FS 诱导 RHA 和 RLA 大鼠中边缘皮质系统不同区域的 BDNF 和 trkB 蛋白水平发生了非常迅速和明显的变化。因此,(1)在 VTA 和 Acb 核区,FS 引起 RHA 大鼠而非 RLA 大鼠的 BDNF 和 trkB-LI 显著增加,而在 Acb 壳区,BDNF 和 trkB-LI 在线和处理方面没有明显变化;(2)在 RLA 大鼠中,IL/PL 皮质的 BDNF-LI 和 ACg 皮质的 trkB-LI 的基础水平明显低于 RHA 大鼠;此外,FS 增加了 RLA 大鼠的 IL/PL 和 ACg 皮质中的 BDNF 和 trkB-LI,但降低了 RHA 大鼠的相应水平。这些结果有力地证明了遗传背景会影响应激对 BDNF/trkB 信号的影响,并支持了这样一种观点,即相同的应激源可能会对不同脑区 BDNF 的表达产生不同的影响。